Insights into the anticancer and anti-inflammatory activities of curcumin-loaded quercetin nanoparticles: in vitro bioassays coupled with synchrotron infrared microspectroscopy†

Abstract

Curcumin (CUR) is an important phytochemical with diverse pharmacological activities, particularly in cancer treatment and inflammation management. However, its poor water solubility and rapid metabolism in vivo have limited its therapeutic potential, inspiring the development of delivery systems such as those based on nanotechnology. Previously, we reported that partial oxidation of the plant polyphenol quercetin (QCT) creates an amphiphilic material that self-assembles into discrete nanoparticles (NPs), either alone or with other polymers. Here we developed a nanoparticle (NP) formulation for CUR based on partially oxidized QCT (oxQCT). The NPs were co-formulated with D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) to enhance their physicochemical properties and potentially synergize with CUR in inducing cancer cell death and alleviating inflammation. CUR was entrapped in oxQCT/TPGS NPs via nanoprecipitation, yielding spherical NPs (87 nm) with 72% loading efficiency, high colloidal stability, and sustained release at physiological pH. The anticancer activity of CUR NPs was evaluated in MCF-7 cells as a model breast cancer cell line, where the oxQCT/TPGS vehicle synergized with free CUR in inducing cell death and promoted its cellular uptake. In RAW 264.7 macrophages, the NPs outperformed free CUR in anti-inflammatory assays by exhibiting stronger reactive oxygen species (ROS) scavenging activities and attenuating the expression of proinflammatory cytokines. We complemented the biological assays with synchrotron-Fourier transform infrared microspectroscopy (SR-μFTIR), which provided insights into biochemical changes in the lipid and protein compositions of MCF-7 and RAW 264.7 macrophages treated with CUR NPs. Our findings present a promising nanoformulation for CUR which can enhance its activity against cancer and inflammation, and highlight the importance of bioanalytical techniques such as SR-μFTIR in discerning the bioactivities of multimodal nanotherapeutics.